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Richard B. Weinberg, MD
Professor, Internal Medicine - Gastroenterology and Physiology & Pharmacology; Associate in Biochemistry
Associate Director, General Clinical Research Center
Email: weinberg@wfubmc.edu
Education:
Harvard University: AB, 1971
Johns Hopkins University: MD, 1975
University of Chicago Hospitals and Clinics, Residency, 1975-78
University of Chicago Hospitals and Clinics, Fellowship, 1978-81
Board Certifications:
American Board of Internal Medicine, 1978
American Board of Internal Medicine/Gastroenterology, 1981 |
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Research Interests: Biophysical aspects of Lipid-Protein Interactions, Lipoprotein Metabolism, Dietary Effects on Human Lipid Metabolism, Diet-Gene Interactions
Current Research:
Research in our laboratory is focused upon the elucidation of the structure and function of human apolipoprotein A-IV (apo A-IV), a 46 kD intestinal protein that is synthesized during lipid absorption and incorporated into the surface of nascent chylomicrons. We have found that apo A-IV possesses dynamic interfacial properties that are optimal for stabilizing surface tension at lipid/aqueous interfaces. We propose that by controlling lipid packing in the surface of expanding chylomicrons, apo A-IV can modulate the efficiency of intestinal lipid absorption.
We utilize a broad array of biophysical techniques to study structure-function relationships of apo A-IV. We use UV, fluorescence, and circular dichroism spectroscopy to probe the effect of naturally occurring and recombinant apo A-IV mutations on its molecular structure. We use sophisticated surface chemistry techniques, such as oil-drop tensiometry, to examine how structural alterations in apo A-IV affect its ability to stabilize expanding lipid surfaces.
A second arm of our research examines the functional genomics of apo A-IV. We use human apo A-IV transgenic and knock-out mice to examine the impact of apo A-IV expression and structure on intestinal triglyceride absorption. We also study the interaction of diet and human genetic apo A-IV polymorphisms on triglyceride metabolism in the General Clinical Research Center.
We expect that these studies will provide novel insights into the biological function of apo A-IV, the complex process of intestinal lipid absorption, and the impact of apo A-IV polymorphisms on lipid metabolism. This research has been continuously funded by the National Heart, Lung, and Blood Institute for over 20 years. Opportunities exist for both pre and post-doctoral study.
Recent Publications:
Beckstead JA, Wong K, Gupta V, Wan CP, Cook VR, Weinberg RB, Weers PM, Ryan RO. The C terminus of apolipoprotein A-V modulates lipid-binding activity. J Biol Chem. 2007 May 25;282(21):15484-9. Epub 2007 Mar 31.
Wong WM, Gerry AB, Putt W, Roberts JL, Weinberg RB, Humphries SE, Leake DS, Talmud PJ. Common variants of apolipoprotein A-IV differ in their ability to inhibit low density lipoprotein oxidation. Atherosclerosis. 2007 Jun;192(2):266-74. Epub 2006 Sep 1.
Ledford AS, Weinberg RB, Cook VR, Hantgan RR, Shelness GS. Self-association and lipid binding properties of the lipoprotein initiating domain of apolipoprotein B. J Biol Chem. 2006 Mar 31;281(13):8871-6.
Lu S, Yao Y, Cheng X, Mitchell S, Leng S, Meng S, Gallagher JW, Shelness GS, Morris GS, Mahan J, Frase S, Mansbach CM, Weinberg RB, Black DD. Overexpression of apolipoprotein A-IV enhances lipid secretion in IPEC-1 cells by increasing chylomicron size. J Biol Chem. 2006 Feb 10;281(6):3473-83. Epub 2005 Dec 7.
Alexander ET, Bhat S, Thomas MJ, Weinberg RB, Cook VR, Bahradwaj MS, Sorci-Thomas MG. Apolipoprotein A-I helix 6 negatively charged residues attenuate lecithin-cholesterol acyltransferase (LCAT) reactivity. Biochemistry 44:5409-5419, 2005.
Publications:
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine |